Substituted [(alpha-nitroalkyl)benzylthio] alkylamines



methylene,

3,166,572 SUBSTITUTED [(oc-NITROALKYL)BENZYLTHIO] Robert C. Tweit, Wilmette, 11]., assignor to G. D. Searle & Co., Chicago, 111., a corporation of Delaware No Drawing. Filed Sept. 10, 1962, Ser. No. 222,614 20 Claims. (Cl. 26034'0.5)

weight less than 100, or a lower alkyl, nitro, methoxy,

cyano, or trifiuoromethyl radical, A and B together can comprehend a methylenedioxy group, R, R, and R can be hydrogen or a lower alkyl radical, and Alk represents a lower alkylene radical.

- The loweralkyl radicals represented by the A, B, C, R, R, and R" terms are typified by methyl, ethyl, propyl,

butyl, pentyl, hexyl, heptyl, and the branched-chain isomers thereof. The term All; comprehends lower alkylene radicals such as methylene, ethylene, trimethylene, tetrapentamethylene, and the branched-chain groups isomeric therewith. The halogens contemplated by the A, B, and C symbols are fluorine, chlorine, and bromine.

A process suitable for the manufacture of the compounds of this invention involves the addition of a mercaptoalkylamine hydrochloride to a substituted B-nitrostyrene, as is illustrated below:

free bases can be isolatedtherefrom by methods wellknown to those skilled in the art. As. a specific example of the instant process, fl-nitrostyrene in methanol is treated with 2mercaptoethylami'ne hydrochloridein the presence of a catalytic quantityof pyrrolidine to yield 2-.['(O-I1ltl'0- 3,166,572 Patented J an. 1 9,

-methyl)benzyltliiojethylamine hydrochloride. Neutralization of the latter salt, typically with aqueous sodium carbonate, results in 2-[(a nitromethyl)benzylthio]ethylamine.

Equivalent to the organic bases of thisinvention are the corresponding non-toxic acid and quaternary salts, for example the citrate, tarti ate, maleate, ascorbate, gluconate, lactate, succinate, phosphate, sulfate, hydrobromide, hydrochloride, 7 me'thiodide, ethiodide, methochloride, methobromide, methosulfat'e, and ethosulfate.

The compounds of this invention are anti-bacterial and anti-fungal agents as is evidenced by their ability to inhibit the growth of Bacillus subtilis, Escherichia coli, Salmonella typhosa, Aspergillus niger, and Trichophyton mentzzgrophytes. They possess also anti-inflammatory activity as is indicated by their inhibition of the edema associated with inflammatory states. compounds are able to suppress appetite by action on the central nervous system. 7

The invention will appear more fully fromthe examples which follow. These examples are set forth by way of illustration only and it will be understood thatthe invention isnot to be construed as limited in spirit or in scope by the details contained therein, as many modifications-in materials'and methods will be apparent from this disclosure'to those skilledinthe art In these examples, temperatures are given in degrees centigrade C.). Quantitiesof materials are expressed in parts i by weight unless otherwise noted.

This application isa continuation-in-part of my copending application, Serial Number 14,492, filed March 14, 1960, and now abandoned.

Example I To a solution of parts of B-nitrostyrene in 300 parts of methanol is added 40 parts of Z-mercaptoethylamine hydrochloride and one part of pyrrolidine. This mixture is warmedto achieve homogeneity, then is filtered through diatomaceous earth. 'Thecrystals which separate on cooling are collected by filtration and dried to afford 2-[(a-nitromethyl) benzylthio]ethylamine hydrochloride, M.P. 152.5-154.5. This compound is represented by the structural formula'.

-CII-CH2NO3 l -HCl SCHQCHZNHQ Example 2 A mixture of 9.7 parts of 3, ;3-dinitrosty rene with 80 a parts of methanol is warmed to achieve solution, then is treated with 5.6 parts .of Z-mercaptoethylamine hydrochloride and 0.1 partof pyrr'cilidine. This wanm solution is filtered throughi'diatomaceous earth, then is concentrated and cooled, resulting in crystallization of the product. Recrystallization from methanol affords pure 2- (a-nitromethyl -3 -nitrobenzylthio] ethylamine hydrochloride, M.P. 129135. It is represented by the structural formula v I i i or ' Example 3 results-in crystallization of the product, which is collected 7 i v by filtration anddried t0 afiord 2-[(a-nitromethyD-4-chlo- In addition, these,

robenzylthio]ethylamine hydrochloride, M.P. 133.5. Its structure is illustrated below:

s CH CH NHg Example 4 To a mixture consisting of 4.8 parts of 3,4-methylenedioxy-fi-nitrostyrene, 2.8 parts of 2-mercaptoethylamine hydrochloride, and 16 parts of methanol is added 0.15 part of pyrrolidine. The reaction mixture is stirred until homogeneous, then is stored at room temperature for about 24 hours, and finally is treated with ether and heated gently. The resulting crystals are collected by filtration and dried to afford 2-[(a-nitromethyl)- 3,4- methylenedioxybenzylthio]ethylamine hydrochloride, M.P. 147l53 (dec.). This substance is represented by the structural formula CHCH2N02 -HC1 s CHBOHZNHZ Example 5 A mixture of 4.1 parts of 4-methyl-p-nitrostyrene, 2.8 parts of Z-mercaptoethylamine hydrochloride, 0.15 part of pyrrolidine, and 12 parts of methanol is warmed until homogeneity is achieved, then is filtered through diatomaceous earth. Dilution of the filtrate with ether initiates crystallization of the product, which is removed by filtration and recrystallized from methanol-ether to afford pure 2- (a-nitromethyl) -4-methylbenzylthio] ethylamine hydrochloride, M.P. 155-157". It is represented by the structural formula S CHgC HzNHg Example 6 A mixture of 4.9 parts of 4, 8-dinitrostyrene, 2.8 parts of 2-mercaptoethylamine of hydrochloride, 0.15 part of pyrrolidine, and 28 parts of methanol is heated to the reflux temperature, then is filtered through diatomaceous earth. The filtrate is concentrated to approximately onehalf volume, then is cooled,v and the resulting crystals are isolated by filtration, then dried to yield 2-[(a-nitromethyl) 4 nitrobenzylthio] ethylamine hydrochloride, M.P. 155156 (dec.). Its structural formula is illustrated below:

omQ-orr-orrmoa A I -HC1 CHZCHQNHZ Example 7 A mixture containing 2.9 parts of 4-methyl-3,;3-dinitrostyrene, 1.4 parts of 2-mercaptoethylamine hydrochloride, 0.15 part of pyrrolidine, and 12 parts of methanol is heated gently until complete solution occurs, then is filtered through diatomaceous earth. The filtrate is diluted with ether, and the resulting crystals are collected by filtration, then dried to afford 2-[(a-nitromethyl)-4- methyl-3-nitrobenzylthio]ethylamine hydrochloride, M.P. 157-l61 (dec.). This compound is represented by the structural formula CH3- -CHCH1NOg I -HC1 SCHgCHzCHgNHg Example 8 A mixture of 5.7 parts of 4-chloro-3,fl dinitrostyrene, 2.8 partsof 2-mercaptoethylamine hydrochloride, and 8 parts of methanol is treated with 0.15 part of pyrrolidine. The resulting solution is filtered and the filtrate is treated with ether to precipitate the product. Recrystallization from acetone affords pure 2-[(a-nitrornethyl)-4-chloro-3- nitrobenzylthio]ethylamine hydrochloride, M.P. 187- 188 (dec.), as represented by the structural formula -HC1 SCH CH NH Example 9 H4 Q JHO.

S 0 H1O HzNHg Example 10 To a mixture of 9.7 parts of 3,fi-dinitrostyrene, 8.5 parts of N,N-diethyl-2-mercaptoethylamine hydrochloride, and 40 parts of methanol is added 0.15 part of pyrrolidine, whereupon the mixture becomes homogeneous. This solution is filtered through diatomaceous earth, and the filtrate is diluted with ether. The resulting crystals are collected by filtration, then recrystallized from methanolether to afford pure N,N-diethyl-2-[(a-nitromethyl)-3- nitrobenzylthio]ethylamine hydrochloride, M.P. 133- 134.5 (dec.). This amine salt is represented by the structural formula N O; CHCH NO;

I 0 H2 C H S 0 H3 C H N H Cl CH; CH;

Example 11 A mixture of 4.4 parts of fl-ethyl-fi-nitrostyrene, 4.5 parts of N,N-diethyl-3-mercaptopropylamine, 15 parts of methanol, and 0.15 part of pyrrolidine is warmed on a steam bath, then is stored at room temperature for about 24 hours. The reaction mixture is filtered through diatomaceous earth, and the filtrate is diluted with ether to produce N,N-diethyl-3-[al-nitropropyl)-benzylthio] propylamine hydrochloride. This substance is represented by the structural formula CHgCHg s-omomomN 4101 CHzCH Example 12 A mixture of 4.05 parts of B-methyl-B-nitrostyrene, 3.5 parts of N-ethyl-2-merc'aptoethylamine hydrochloride, 0.15 part of pyrrolidine, and 10 parts of methanol is allowed to stand at room temperature for about 24 hours, then is filtered through diatomaceous earth, and the filtrate is diluted with ether. The resulting preciptate is collected'by filtration to yield'N-ethylJ[a-(l-nitroethyl).

substance is -H.Ol SOH GH NH; Y

Example 23 A mixture of parts of 4-fluorobenzaldehyde, 3 parts of ammonium carbonate, 11.4 parts of nitromethane, and 31.5 parts of acetic acid is heated at the reflux temperature for about 1% hours, then is cooled to room temperature. The resulting crystals are collected by filtration and dried, resulting in 4-fluoro-fi-nit'rostyrene, which melts at about 96- 99. V

A mixture of 5 parts of 4-fluoro-B-nitrostyrene, 3.4 parts of Z-mercaptoethylamine hydrochloride, 12 parts of methanol, and 0.1 part'of pyrrolidine is allowed to react according to the procedure described in Example 1, thus producing 2 [(a nitromethyl)-4-flu0robenzylthio] ethylamine hydrochloride, melting at about 163-166 (dec.).-

This compound is characterized further by the structural formula Example 24 sure to afford 2,4-dimethyl-B-nitrostyrene, boiling at 119- 126 at 0.2 mm. pressure.

A mixture of 17.7 parts of 2,4-dimethyl-B-n.itrostyrene, 11.4 parts of Z-mercaptoethylamine hydrochloride, 0.15 part of pyrrolidine, and 12 parts of methanol is allowed to react according to the processes described in Example 1 in order to afford 2-[(a-nitromethyl)-2,4-dimethylbenzylthio]ethylamine hydrochloride, which substance melts at about 130-137 with decomposition. It is represented by the structural formula SCHgCHgNHQ Example 2 5 A mixture of 19.1 parts of 4-isopropyl-fi-nitrostyrene, 11.4 parts of 2-mercaptoethylamine hydrochloride, 0.1'5 part of pyrrolidine, and 16 parts of methanol is allowed to react by the procedure described in Example I to afford 2 [(a'- nitromethyl) 4 isopropylbenzylthio]ethylamine hydrochloride, melting at about 135-138. This substance is represented by the structural formula CHQ GH-QA JH-G N Hot somonzNm V Example 26 I A mixture of 19.8 parts of 4 chloro-B-methyl-i8-nitrostyrene, 11.4 parts of Z-mercaptoethylamine hydrochloride, 0.15 part of.pyrrolidine, and 16 parts of methanol is allowed to react according to the processes described in W .Example 1, thus affording 2-[a-(1-nitroethy1)-4-chloro-. IbenZyIthioJethyIamine hydrochloride, melting at about .8 a. 131135 and characterized further by the structural formula 1 e 1 CH3 v 01+-c11*dH-N01 somoHzNH, Example 27 A mixture of 50 parts of 2-chlorobenzaldehyde, 50 parts of l-nitropropane, 10 parts of ammonium carbonate, and 157.5 parts of acetic acid is heated at the reflux temperature for about 8 hours, then is partially concentrated at reduced pressure and poured onto crushed ice. The organic layer is separated, washed successively with aqueous sodium bisulfite, aqueous sodium carbonate, and water, then dried over anhydrous sodium sulfate, and. stripped of solvent to afford 2-ch1oro-18-ethyl-,8-nitrostyrene as an oil.

To 190 parts by volume of fuming nitric acid is. added, with cooling and stirring, 63.5 parts of 2-chlord-fl-ethyl- ,B-nitrostyrene, and this reaction mixture is stirred for about one hour, then is poured onto crushed ice. The

. resulting aqueous mixture is extracted With ether, and

the organic layer is washed with water, dried over anhydrous sodium sulfate, and concentrated to dryness at reduced pressure. Recrystallization of the residue from ethanol affords 2-chloro-fl-ethyl 5,;3-dinitrostyrene as a low-melting solid. V r I A mixture of 8.7 parts of 2-chloro- 3-ethyl-5,fl-dinitrostyrene, 3.8 parts of Z-mercaptoethylamine hydrochloride, 0.2 part of pyrrolidine, and 16 parts of methanol is allowed to react by the procedure described in Example 1, resulting in 2-[a(l-nitropropyl)-2-chloro-5-nitrobenzylthio]ethylamine hydrochloride, melting at about 177- 179 and characterized further by the structural formula l CHZCHQ CH-H-NOn I .-HG1 S CH CH NH N0,

Example 28 1 A mixture of 13.9 parts of 2 -chloro-5,B-dinitrostyrene,

6.8 parts of 2-mercaptoethylamine hydrochloride, 16 parts 7 of methanol, 14 parts of ether, and 0.25 part of pyrrolidine is allowed to react by the procedure described in Example 1 to aiford 2-[(a-nitromethyl)-2-chlor05-nitrobenzy1- thio]ethylamine hydrochloride, melting at about 180- 182. This substance is represented by the structural formula Q-C JH-omNO, H s amend 1H,.

' Example 29 h A mixture of 7.65 parts of 2-fluoro-5,fi-dinitrostyrene,

4 parts of 2-rnercaptoethylah1ine hydrochloride, 8 parts QTOHOEHNOQ llroz S CHzCHzNHg Example 30 A mixture of 4.7 parts of 2-bromo-5,/3-dinitrostyrene,

benzylthiolethylamine hydrochloride, which is represented 1 by the structural formula Example 13 Example 14 A mixture of 9.7 parts of 3,5-dinitrostyrene, 11.2 parts of N,N-di-n-butyl-2-mercaptoethylamine hydrochloride, 0.15 part of pyrrolidine, and I 50 parts of methanol is heated gently, then is filtered through diatomaceous earth. The cooled filtrate is diluted with ether, resulting in precipitation of the product, N,N-di-n-butyl-2-[(ot-nitromethyl)-3-nitrobenzylthio]ethylamine hydrochloride. This compound is represented by the structural formula sornornN ct-rlcrrromorra Example 15 The substitution of 6.4 parts of 3-mercaptopropylamine hydrochloride in the procedure of Example 3 results in 3-[(a-nitromethyl)-4 chlorobenzylthio]propylamine hydrochloride of the structural formula Example 16 A mixture of 4.4 parts of 3,4-dichloro-fl-nitrostyrene, 2.3 parts of Z-mercaptoethylamine hydrochloride, 24 parts of methanol, and 0.15 part of pyrrolidine is allowed to react according to the procedure of Example 1, resulting in 2-[(a-nitromethyl) 3,4 dichlorobenzylthio]ethylamine hydrochloride, melting atabout .174177 (dec.). It is represented by the structural formula Example 17 The reaction of 7.2 parts of 2,4-dichloro-B-nitrostyrene, 2.3 parts of 2-mercaptoethylamine hydrochloride, 24 parts of methanol, and 0.15 part of pyrrolidine is allowed to react according to the processes described in Example 1 to afford 2-[(oc nitromethyl)-2,4-dichlorobenzylthio]ethylamine hydrochloride, melting at about 113.5-117". This substance is represented by the structural formula 6 Example 18 To a solution of 5.5 parts of 3-ch1oro-fi-nitrostyr'ene in 17.5 parts of ether is added successively a solution of 3.4 parts of 2-mercaptoethylamine hydrochloride in 20 parts of methanol and 0.1 part of pyrrolidine. This reaction mixture is allowed to react by the procedure described in Example 1, resulting in 2-[(a-nitromethyl)-3-chlorobenzylthioJethylamine hydrochloride, melting at about 117.5- l20. It is represented by. the structural formula 01 Q-CEE-OJLNO;

l 4101 s CH CH NH;

Example 19 The reaction of 5 parts of 2-chloro-fl-nitrostyrene, 3.4 parts of Z-mercaptoethylamine hydrochloride, 16 parts of methanol, and 0.15 part of pyrrolidine by the processes described in Example 1 results in 2-[(m-nitromethyl)-2 chlorobenzylthio]ethylamine hydrochloride, which substance melts at about 109113 and is characterized further by the structural formula S CHgCHgNHg Example 20 A mixture of 6.8 parts of '4-bromo- 8-nitrostyrene, 3.4 parts of Z-mercaptoethylamine hydrochloride, 16 parts of methanol, 7 parts of ether, and 0.15 part of pyrrolidine is allowed to react by the procedure of Example 1 to afford 2-[ (a -nitromethyl) -4-bromobenzylthio] ethylamine hydrochloride, melting at about -181 (dec.). This substance is characterized further by the structural formula Example 21 A mixture of 5 parts of 2-fluoro-fl-nitrostyrene, 3.4 parts of Z-mercaptoethylamine hydrochloride, 8 parts of methanol, and 0.15 part of pyrrolidine is allowed to react by the'procedure of Example 1 to produce 2-[(a-nitromethyl) 2 fluorobenzylthio]ethylamine hydrochloride, melting at about -11711 9 and represented by the structural formula S CH2 CHzNHg Example 22 To 30 parts by volume of fuming nitric acid is added, with stirring and cooling, 10 parts of 2-chloro-fi-methy1- fl-nitrostyrene, and the resulting solution is allowed to stand at room temperature for about 16 hours, then is poured into a mixture of ice and water. The resulting precipitate is collected by filtration, then is dried and dissolved in benzene. This organic solution is chromatographed on a silica gel column, and the benzene eluate is evaporated to dryness to afford a residue which is crystallized from acetone-methanol, resulting in 2-chloro- B-methyl-Sfi-dinitrostyrene, M.P. about 64-67.

A mixture of 3 parts of 2-chloro-B-methyl-5,fl-dinitrostyrene, 1.4 parts of 2-rnercaptoethylamine hydrochloride,

oaomNoz norv S CHZCHZNHZ Y 3N O 2 Example .31

To a mixture of Sparts of ammonium carbonate, 11.4 parts of nitromethane, and 31.5 parts of acetic acid is added 10.3 parts of Z-methoxy-S-nitrobenzaldehyde, and theresulting reaction mixture is heated at the reflux temperature for about one hour/then is cooled. The resulting crystalline product which separates is collected by filtration, dried, and recrystallized from acetone to produce Z-methoxy-S,fl-dinitrostyrene, melting at about 174- 176. 1 a

A mixture of 5.6 parts of 2-methoXy-5,,B-dinitrostyrene, 2.8 parts of Z-mercaptoethylamine hydrochloride, 16 parts of methanol, 7 parts of ether, and 0.1 part of pyrrolidine is allowed to react by the procedure described in Example 1, resulting in 2-[(a-nitromethyl)-2-methoxy-5-nitrobenzylthio]ethylamine hydrochloride, which substance melts at about 163 -166" with decomposition. It is characterized further by the structural formula Example 32 p A mixture of 3.85'parts of 4-cyano-fl-fnitrostyrene, 2.5 parts of 2-rriercaptoethylamine hydrochloride, 8 parts of methanol, and 0.15 part of pyrrolidine is stirred until solution occurs, then .is filtered through diatomaceous earth, and is diluted with ether. The resulting solid which precipitates is collectedby filtration and dried to afford 2 [(cc nitromethyl) 4 cyanobenzylthio1ethylamine hydrochloride, melting at 'about l66169. This compound is represented by the'structural formula 3 No c incnmo.

S CHz HzN 2 Example 33 A mixture of 13 parts of 2-chloro-5-ethyl-5,p-dinitro- -HOl styrene, 7 parts of N,N-dimethyI-Z-mercaptoethylamine' hydrochloride,.0.15 part of p-yrrolidine, and 20 parts "of methanolis stirred until solution occurs. Approximately 35 parts of ether is added and the resulting precipitate is removed by filtration. The filtrate is again diluted With ether, and the product. which crystallizes is collected by filtration, then is recrystallized from methanol-ether to afford N,N-dimethyl-2-[a-'(l-nitropropyl)-2-chloro-5- nitrobenzylthio]'ethylamine hydrochloride, melting at about 155l58. This compound is represented by the structural formula due, is extracted into ether. This organic solution is by distillation atreduced pressure andpthe resulting resi- 10 washed successively with water, aqueous sodium bisulfite, and aqueous sodium bicarbonate, then is dried over anhydrous sodium sulfate and concentrated at reduced pressure. This residue is then added slowly to parts by volume of fuming nitric :acid, with cooling and stirring, and stirring is continued for about one hour longer, after which time the reaction mixture is poured into ice and water. The resulting aqueous mixture is extra'ctedwith methylene chloride, and the organic extract is washed 7 with water, then is dried and concentrated at reduced,

pressure. This residue is filtered through diatomaceous earth to yield 2-chloro-B-propyl-5,B-dinitrostyrene as an oil.

A mixture of 8.1 parts of 2-chloro-fi-propy1-5,,8-dinitrostyrene, 3 parts of Z-mercaptoethylamine hydrochloride,

I CH2CHZCH3 I S CIiIgCHgNHg N02 1 Example 35 p A mixture of 25 parts of 2,6-dichlorobenzaldehyde, 25

*parts'of l-nitropropane, 5 parts of ammonium carbonate,

and 78.75 partsot acetic acid is heated at the reflux temperature for about 8 hours, then is cooled and poured onto crushed ice.

cantation, and the residual oil is dissolved in ether. This organic solution is washed successively with'water, aque- The aqueous layer is separated by'rdeous sodium bisulfite, and water, then'is dried over anhydrous sodium sulfate and evaporated to dryness in an atmosphere of nitrogen. The resulting residue solidifies on cooling to afford 2,6-dichloro-f3 ethyl-,B-nitrostyrene.

A mixture of 8.5 parts of 2,6-dichloro ,8-ethyl-5-nitro- I styrene, 3.4 parts of Z-mercaptoethylamine hydrochloride,

0.15 part of pyrrolidine, and 4 parts of methanol is heated on the steam bath to eifect homogeneity, and the resulting solution is kept at room temperature for several hours. Ether is then added, and the initial precipitate is removed by filtration. The" further addition of ether results in crystallization of the product, which is collected 'by filtration and dried, resulting in 2-[a-(l-nitropropyl)- 2,6-dichlorobenzylthio] ethylamine hydrochloride, melting at about 133. This compound is represented 'bythe structural formula Example 36 ing'.and stirring, and stirring is continued for aboutv one hour longer. The reaction mixtureis. thenpoured onto crushed ice, and the resulting aqueous, mixture is extracted with methylene chloride. The methylene chloride extracts a're washed with water, dried, over anhydrous sodium sulfate, and concentrated to dryness to afford a residue,

.which is recrystalliz ed' from methanol, resulting in 2,6-

dichlor-o fi-ethyl-3 ,,B-dinitrostyrene, melting at about 102- -1 6 9 I I p j A mixture orsgs parts of 2,6-dichloro-B-ethyl3,fi dinitrostyrene, 2.3pai7ts' of Z-me rcaptQethYyIamine hydro- 1 1 chloride, 0.15 part of pyrrolidine, and 8 parts of methanol is stirred at room temperature until solution occurs, at which time the reaction mixture is filtered through diatomaceous earth, and the filtrate is diluted with ether. The resulting crystalline product is collected by filtration and dried to yield 2-[a-(l-nitropropyl)-2,6-dichloro-3 nitrobenzylthioJethylamine hydrochloride, melting at about 196198 with decomposition. It is further characterized by the structural formula I CHzCH;

Example 37 A mixture of 20.4 parts of l-nitrooctane, 18 parts of 2-chlorobenzaldehyde, 31.5 parts of acetic acid, and 2 parts of ammonium carbonate is heated at the reflux temperature for about 23 hours, then is stripped of solvent at reduced pressure. The resulting residue is extracted with ether, and the organic layer is separated, washed successively with water, aqueous sodium bisulfite, and aqueous sodium bicarbonate, then is dried over anhydrous sodium sulfate and concentrated to afford 2-chloro-B-heptyl-5, 3-dinitrostyrene as an oil.

To 100 parts by volume of fuming nitric acid is added 16.8 parts of 2-chloro- 8-heptyl-fi-nitrostyrene, with cooling and stirring. After the addition is complete, the reaction mixture is stirred for about one hour, then is poured onto crushed ice. This aqueous mixture is then extracted With ether, and the organic layer is separated, washed with water, dried over anhydrous sodium'sulfate, and concentrated to an oil. This oil is adsorbed on a silica gel chromatographic column and is eluted with 50% hexane in benzene to afford 2-chloro-fl-heptyl-5,B- dinitrostyrene.

A mitxure of 4.75 parts of 2-chloro-13-heptyl-5,fi-dinitrostyrene, 1.65 parts of Z-mercaptoethylamine hydrochloride, 0.15 part of pyrrolidine, 4 parts of methanol, and 7 parts of ether is heated to achieve solution, then is filtered through diatomaceous earth. The reaction mixture is concentrated at reduced pressure to afford the oily product, 2- [a-( l-nitrooctyl) -2-chloro-5-nitrobenzylthio] ethylamine hydrochloride. This substance is represented by the structural formula A mixture of 25 parts of 4-trifluoromethylbenzaldehyde, 25 parts of l-nitropropane, parts of ammonium carbonate, and 75 parts of acetic acid is heated at the reflux temperature for about 33 hours, then is poured onto crushed ice. The aqueous layer is separated by decantation, then is extracted with ether. The ether extract is combined with the original organic layer, and these combined solutions are washed successively with water, aqueous sodium carbonate, and aqueous sodium bisulfite. This washed solution is dried over anhydrous sodium sulfate and is concentrated to dryness to yield 4-trifluoromethyl-B-ethyl-B-nitrostyrene.

A mixture of 5 parts of 4-trifluoromethyl-p-ethyl-fl-nitrostyrene, 2.1 parts of Z-mercaptoethylamine hydrochloride, 0.15 part of pyrrolidine, and 4 parts of methanol is heated on the steam bath for about one hour, then is cooled and diluted with ether. The resulting precipitate is collected by filtration, then is dissolved in methanol and reprecipitated with ether; The initial crystalline material is separated by filtration and discarded, and the filtrate is allowed to stand until crystallization is complete. The latter material is' collected by filtration and dried to i 12 afford 2- [a( l-nitropropyl -4-trifiuoromethylbenzylthio] ethylamine hydrochloride, melting at about 162-165 with decomposition. This compound is represented by the structural formula CH3 CH(IIHNOZ SCH CH NH Example 40 The substitution of 17.1 parts of 3-methylbenzaldehyde in the procedure of Example 38 results in Z-[a-(I-nitropropyl)-3-methylbenzzylthio]ethylamine hydrochloride of the structural formula CH CHa CH tH NO,

s oHgcHgNHz-Hcl Example 41 -HCl By substituting 64.2 parts of 3-cyano-fl-nitrostyrene and otherwise proceeding accordingto the procedure of Example 1, 2-[(a-nitromethyl) 3 cyanobenzylthio1ethy1- amine hydrochloride is obtained. This compound is represented by the structural formula CH C HZN 0 a S CHQCHZNHZHCI Example 42 The substitution of 71.6 parts of 2,;3-dinitrostyrene in the procedure of Example 1 results in 2-[ (a-nitromethyD- 2-nitrobenzylthio]ethylamine hydrochloride of the structural formula CHGH NO SCHzCEzNHz-HC] Example 43 By substituting 93.8 parts of 3,4-dimethoxy-6,B-dinitrostyrene and otherwise proceeding according to the processes of Example 1, 2-[(a-nitromethyl)-3,4-dimethoxy-6- nitrobenzylthio]ethylamine hydrochloride of the structural formula OCH;

| SCHgCHzNHi NO, I

is obtained.

What is claimed is: 1. A compound of the formula A B R @on-bn-No,

SAIk- N wherein A, B, and C are selected from the group consisting nitro] ethylamine,

of hydrogen, halogens of atomic weight less than 100, lower alkyl, nitro, methoxy, cyano,'a'nd trifluoromethyl radicals, A and B together comprise a methylenedioxy radical, R, R, and R are selected from the group consisting of hydrogen and lower alkyl' radicals, and Alk is 'a lower alkylene radical.

2. 2-[ a-nitromethyl) benzylthio] ethylamine.

3. 2-[(a nitromethyl)-3,4-methylenedioxybenzylthio] ethylamine.

4. Z-[oz-(l nitroethyl)-2-chlorobenzylthio]ethylamine.

5. N,N-diethyl-2-[(a nitromethyl) 3-nitrobenzyltl1io] ethylamine. a

6 2-[(a-nitromethyl) 3,4 dichlorobenzylthio1ethylamine.

v 7. 2-[( x-nitromethyl) 4 isopropylbenzylthio]ethyl-- amine.

8. 2-[u-(1 nitroethyl)-4-chlorobenzylthio]ethylamine. 9. N,N dimethyl-[u-(l --nitropropyl). 2 chloro-S- 10. 2-[cc-( 1 nitropropyl) 2,6 dichloro 3 nitrobenzylthio] ethyl amine.

11L Z-[oc-(l nitropropyl) 2,6 dichlorobenzj lthio] ethylamine.

12. A compound of the formula A @on-onmo,

1 wherein A is a halogen of atomic weight less than 100 and All; is a l'ower alkyleneradical.

13. 2-[(oc nitromethyl) 4 chlorobenzylthio1ethylamine. k V

14. 2-[(oc nitromethyl) 4- bromobenzylthio]ethylamine. v V

15 ethylamine.

14 I t I5. 2'-[(r nitromethyl) 2 fiuorobenzy1thi01ethylamine. i 16. A compound of the formula I C1 I (lower alkyl) 4321-3211: On C Hg 0 HgNHg N 02 V 17. 2-[a -(1 nitroethyl) 2 chldro-S-nitrobnzylthio] ethylamine.

l8. 2-[|x(l nitropropyl) 2 chldro-S-nitrobenzylthioj ethylamine. r a

19. 2-[06-(1 nitrobutyl) 2 chloro-S-nitrobenzylthio] Bahner June 19, 1950 2,511,961 2,523,233 Prill Sept. 19, 1950 2,769,839 Fincke n Nov. 6, 195

OTHER REFERENCES Cason et a1.: L'Am. Chem. Soc., yol 73, pp. 142-145 35 (1951), QD A 5.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3,166 ,572 January 19, 1965 Robert c. Tweit It is hereby certified that'error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 3, line 41', strike out "of", second occurrence; column 4, line 14, for "pyrolidine" read pyrrolidine samecolumn 4, lines 62 to 65, the formula should appear as shown below insteadof as in the patent:

CH2CH3 -CHZCH2CH2 CH2CH3 column 9, lines 4 to 9, the formula should appear as shown below instead of as in the patent:

HCHZNOZ 'HCl N0 SCI-I CH NH column ll, lines 47 to 51, the formula should appear as shown below instead of as in the patent:

Cl CH CH CH CH CH CH CH H-CH-NO v .HCl

SCI-I CH NH column 12, line 24, for "methylbenzzylthio" read methylbenzylthio Signed and sealed this 22nd day of June 1965.

(SEAL) Attest:

ERNEST W. SWIDER EDWARD J. BRENNER Attesting Officer Commissioner of Patents 

1. A COMPOUND OF THE FORMULA 